Metabolipidomic profiling reveals an age‐related deficiency of skeletal muscle pro‐resolving mediators that contributes to maladaptive tissue remodeling

Markworth, James F.; Brown, Lemuel A.; Lim, Eunice; Castor-Macias, Jesus A.; Larouche, Jacqueline; Macpherson, Peter; Davis, Carol; Aguilar, Carlos A.; Maddipati, Krishna Rao; Brooks, Susan V.

doi:10.1111/acel.13393

Cited by 34 publications

(23 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with previous observations in an analogous model in the rectus femoris (10,25), defects below the critical threshold regenerate, while larger defects result in long-term increases in fibrosis and reductions in contractile force. Using this model of regenerative and degenerative VML, we performed metabolipidomics analysis (40) over a time course to understand signaling factors that contribute to the observed changes in fibrosis. We detected a stark imbalance of pro-inflammatory eicosanoids to pro-resolving lipid mediators in degenerative VML injuries, which correlates with our previous observations of sustained inflammation and persistent neutrophil (10) and macrophage (6) presence following degenerative VML.…”

Section: Discussionmentioning

confidence: 99%

Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss

Castor-Macias

Larouche

Wallace

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

The acute traumatic or surgical loss of skeletal muscle, known as volumetric muscle loss (VML), is a devastating type of injury that results in exacerbated and persistent inflammation followed by fibrosis. The mechanisms that mediate the magnitude and duration of the inflammatory response and ensuing fibrosis after VML remain understudied and as such, the development of regenerative therapies has been limited. To address this need, we profiled how lipid mediators, which are potent regulators of the immune response after injury, varied with VML injuries that heal or result in fibrosis. We observed that non-healing VML injuries displayed increased pro-inflammatory eicosanoids and a lack of pro-resolving lipid mediators. Treatment of VML with a pro-resolving lipid mediator synthesized from docosahexaenoic acid, called Maresin 1, ameliorated fibrosis through reduction of neutrophils and macrophages and improved myogenesis, leading to enhanced recovery of muscle strength. These results expand our knowledge of the dysregulated immune response that develops after VML and identify a novel immuno-regenerative therapeutic modality in Maresin 1.

show abstract

Section: Discussionmentioning

confidence: 99%

Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss

Castor-Macias

Larouche

Wallace

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, Resolvin D1 (RvD1), which is another member of the D-series resolvin family, was shown to limit neutrophil infiltration into the peritoneum (2) and reduced neutrophils in the lungs after remote organ ischemia reperfusion injury (4) in old animals. Another study demonstrated that RvD1 treatment to aged mice reduced skeletal muscle inflammation and fibrosis, again suggesting a role for D-Series resolvins in limiting inflammation and tissue injury in aging (28). The mechanisms of actions of RvD1 in aging are not fully known.…”

Section: Discussionmentioning

confidence: 99%

The Resolvin D2-GPR18 Axis Enhances Bone Marrow Function and Limits Hepatic Fibrosis in Aging

Fitzgerald

Bonin

Sadhu

et al. 2023

Preprint

View full text Add to dashboard Cite

Aging is associated with non-resolving inflammation and tissue dysfunction. Resolvin D2 (RvD2) is a pro-resolving ligand that acts through the G-protein coupled receptor (GPCR) called GRP18. Using an unbiased screen, we report increased Gpr18 expression in macrophages from old mice and in livers from elderly humans that is associated with increased steatosis and fibrosis in middle-aged (MA) and old mice. MA mice that lack GPR18 on myeloid cells had exacerbated steatosis and hepatic fibrosis, which was associated with a decline in Mac2+ macrophages. Treatment of MA mice with RvD2 reduced steatosis and decreased hepatic fibrosis, correlating with increased Mac2+ macrophages, monocyte-derived macrophages and elevated numbers of monocytes in the liver, blood, and bone marrow. RvD2 acted directly upon the bone marrow to increase monocyte-macrophage progenitors. Using a transplantation assay we further demonstrated that bone marrow from old mice facilitated hepatic collagen accumulation in young mice, and transient RvD2 treatment to mice transplanted with bone marrow from old mice prevented hepatic collagen accumulation. Together, our study demonstrates that RvD2-GPR18 signaling controls steatosis and fibrosis and provides a mechanistic-based therapy for promoting liver repair in aging.

show abstract

“…Recently, Félix-Soriano et al found that MaR1 was significantly reduced in adipose tissue in aged HFD-induced obese mice compared to young normal controls [ 33 ]. Markworth et al also showed that aged mouse muscle displayed significantly lower MaR1 levels than the young mouse muscle [ 34 ]. These data suggested that ageing is associated with MaR1 deficiency.…”

Section: Discussionmentioning

confidence: 99%

Low serum Maresin-1 levels are associated with non-alcoholic fatty liver disease: a cross-sectional study

Xia

Wang

et al. 2021

Lipids Health Dis

View full text Add to dashboard Cite

Background Maresin-1 (MaR1) is an anti-inflammatory pro-resolving mediator and is considered a potential regulator of metabolic diseases. Non-alcoholic fatty liver disease (NAFLD) is a very common metabolic liver disease. However, little information is available on the relationship between MaR1 and NAFLD in humans. Therefore, the study explored the association between serum MaR1 levels and NAFLD. Methods A cross-sectional study was conducted in 240 Chinese people, including 116 non-NAFLD subjects and 124 NAFLD patients. Serum MaR1 levels were determined by enzyme-linked immunosorbent assay (ELISA). The association between MaR1 and NAFLD was assessed. Results Circulating MaR1 levels in NAFLD patients were markedly lower than those in non-NAFLD subjects (63.63 [59.87–73.93] vs 73.11 [65.12–84.50] pg/mL, P = 0.000). The percentages of patients with NAFLD gradually decreased with the increase of MaR1 quartiles (P < 0.001). Furthermore, serum MaR1 levels were positively associated with aspartate aminotransferase/alanine aminotransferase (AST/ALT), albumin, the albumin-globulin-ratio, and high-density lipoprotein cholesterol (HDL-C) (all P < 0.05) and negatively associated with body mass index (BMI), waist circumference, hip circumference, the waist-to-hip ratio, ALT, gamma-glutamyl transpeptidase (GGT), uric acid, triglyceride (TG), and fasting blood glucose (FBG) (all P < 0.05) after adjusting for sex and age. Binary logistic regression analysis revealed that serum MaR1 levels were significantly associated with NAFLD. Conclusions Circulating MaR1 levels were decreased in patients with NAFLD, and a negative correlation was identified between NAFLD and serum MaR1 concentrations. Decreased MaR1 might be involved in the development of NAFLD.

show abstract

Metabolipidomic profiling reveals an age‐related deficiency of skeletal muscle pro‐resolving mediators that contributes to maladaptive tissue remodeling

Cited by 34 publications

References 45 publications

Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss

Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss

The Resolvin D2-GPR18 Axis Enhances Bone Marrow Function and Limits Hepatic Fibrosis in Aging

Low serum Maresin-1 levels are associated with non-alcoholic fatty liver disease: a cross-sectional study

Contact Info

Product

Resources

About